GZD824-dimesylate-HQP1351-dimesylate-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEGZD824dimesylateCat.No.:HY-15666ACASNo.:1421783-64-3Synonyms:HQP1351dimesylate分⼦式:C₃₁H₃₅F₃N₆O₇S₂分⼦量:724.77作⽤靶点:Bcr-Abl作⽤通路:ProteinTyrosineKinase/RTK储存⽅式:4°C,sealedstorage,awayfrommoistureandlight*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoistureandlight)溶解性数据体外实验DMSO:125mg/mL(172.47mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.3797mL6.8987mL13.7975mL5mM0.2759mL1.3797mL2.7595mL10mM0.1380mL0.6899mL1.3797mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存⽅式和期限。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案，配制前请先配制澄的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的⼯作液，建议您现⽤现配，当天使⽤；澄的储备液可以根据储存条件，适当保存；以下溶剂前的百分⽐指该溶剂在您配制终溶液中的体积占⽐)：1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(2.87mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(2.87mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(2.87mM);Clearsolution1/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性GZD824dimesylate(HQP1351dimesylate)⼀种有⼝服活性的pan-Bcr-Abl抑制剂，除了抑制野⽣型Bcr-Abl(IC50=0.34nM)之外，对突变型Bcr-Abl也具有⼴泛的抑制活性并且对野⽣型。GZD824dimesylate具有抗肿瘤作⽤[1]。IC50&TargetIC50:0.68nM(Bcr-AblT315I),0.27nM(Bcr-AblE255K),0.71nM(Bcr-AblG250E),0.15nM(Bcr-AblQ252H),0.35nM(Bcr-AblH396P),0.29nM(Bcr-AblM351T),0.35nM(Bcr-AblY253F),Bcr-AblF317L[1]体外研究GZD824dimesylateshowsantiproliferativeactivityinstablytransformedBa/F3cellswhosegrowthwasdrivenbynativeBcr-AblorBcr-Ablmutants[1].GZD824dimesylateselectivelyandpotentlyinhibitstheproliferationofBcr-Abl-positiveleukemiacells[1].GZD824dimesylateinhibitsBcr-AblsignalinginK562(1-20nM;4.0hours)andBa/F3stablecelllinesexpressingnativeBcr-Abl(0.1-100nM;4.0hours)orBcr-AblT315I(0.1-100nM;4.0hours)[1].WesternBlotAnalysis[1]CellLine:K562cellsConcentration:1nM,2nM,5nM,10nM,20nMIncubationTime:4.0hoursResult:InhibitedBcr-AblsignalinginK562celllines.体内研究GZD824dimesylatesuppressestumorgrowthinmicebearingallograftedBa/F3cellsexpressingBcr-AblWT[1].GZD824dimesylate(1-20mg/kg;i.g.;daily;for10days)significantlyincreasesthemediansurvivalofthemicebearingallograftedBa/F3cellsexpressingBcr-AblT315I[1].GZD824dimesylateexhibitsagoodoralbioavailability(rat48.7%)andCmax(i.v.1375.6μg/L;oral390.5μg/L)followingadministration(5mg/kgfori.v.;25mg/kgfororal)inrat[1].AnimalModel:SCIDnudemice,bearingallograftedBa/F3cellsexpressingBcr-AblT315I[1]Dosage:1mg/kg,2mg/kg,5.0mg/kg,10mg/kg,20mg/kgAdministration:Oralgavage,daily,for10daysResult:Efficientlyprolongsanimalsurvivalinanallograftleukemiatumormodel.AnimalModel:Rats[1]Dosage:5mg/kgfori.v.;25mg/kgfororal(PharmacokineticAnalysis)Administration:Intravenousinjectionandoraladministration2/3MasterofSmallMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:Oralbioavailability(48.7%),Cmax(1375.6μg/Lfori.v.;390.5μg/Lfororal),T1/2(5.6hourfori.v.;10.6hoursfororal).•BiochimBiophysActa.2018May25;1865(9):1173-1186.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RenX,PanX,ZhangZ,IdentificationofGZD824asanorallybioavailableinhibitorthattargetsphosphorylatedandnonphosphorylatedbreakpointclusterregion-Abelson(Bcr-Abl)kinaseandovercomesclinicallyacquiredmutation-inducedresistanceagainstimatinib.JMedChem.2013Feb14;56(3):879-94.McePdfHeightCaution:Pro